Abstract

Introduction: In recent years, more attention was dedicated to developing new methods for designing of drug delivery systems. The aim of present work is to improve the efficiency of the antibacterial drug delivery process, and to realize and to control accurately the release. Methods: First, graphene oxide (GO) was prepared according to the modified Hummers method then the GO was modified with carboxymethylcellulose (CMC) and Zn-based metal-organic framework (MOF-5) through the solvothermal technique. Results: Performing the various analysis methods including scanning electron microscope (SEM), X-ray diffraction (XRD), EDX, Fourier transform infrared (FTIR) spectroscopy and Zeta potentials on the obtained bio-nanocomposite showed that the new modified GO has been prepared. With using common analysis methods the structure of synthesized materials was determined and confirmed and finally, their antibacterial behavior was examined based on the broth microdilution methods. Conclusion: Carboxymethylcellulose/MOF-5/GO bio-nanocomposite (CMC/MOF-5/GO) was successfully synthesized through the solvothermal technique. Tetracycline (TC) was encapsulated in the GO and CMC/MOF-5/GO. The drug release tests showed that the TC-loaded CMC/MOF5/GO has an effective protection against stomach pH. With controlling the TC release in the gastrointestinal tract conditions, the long-time stability of drug dosing was enhanced. Furthermore, antibacterial activity tests showed that the TC-loaded CMC/MOF-5/GO has an antibacterial activity to negatively charge E. coli bacteria in contrast to TC-loaded GO.

demonstrates FT-IR spectra to characterize CMC, MOF-5, GO and CMC/MOF-5/GO. The symmetric stretching and asymmetric stretching of the carboxylate groups in MOF-5 and CMC were respectively observed at 1508, 1725 cm-1 and 1539, 1401 cm-1. For MOF-5 and GO could be detected the benzene basic vibration at 1630 cm-1. The several bands that can be observed in the region of 1250–600 cm-1 are related to the out-of-plane vibrations of BDC carboxylate groups for MOF-5. All detected characteristic peaks in CMC/MOF-5/GO with growing intensity in comparison with MOF-5 indicate that the structure of MOF-5, CMC and GO were preserved. For interactions between the –COOH of GO, CMC, and BDC with Zn2+ of CMC/MOF-5/GO the FT-IR results could be good evidences.

XRD patterns of the GO, MOF-5, and CMC/MOF-5/GO were shown in . The significant increase of layer spacing with a high degree of orientation of GO was evidenced by border peak at 2θ 11.16° which obvious in the GO XRD spectrum. The XRD pattern of MOF-5 is in good consistency to previous reports (). The broad reflection at 2θ value of about 20° in the CMC/MOF-5/GO XRD pattern is related to the amorphous nature of CMC. Furthermore, the XRD pattern of CMC/MOF-5/GO is similar to the MOF-5, which demonstrates that the MOF-5 structure is preserved. The XRD results proved that the crystalline structure of the MOF-5 component did not distort by the composition of MOF-5, GO and CMC in the CMC/MOF-5/GO bio-nanocomposite.

Element information of samples was obtained using EDX analysis (). The spectrum of CMC () shows signals for the presence of C, O and Na with weight percentages 62.23, 36.68 and 0.89 W%, respectively. The EDX signals for MOF-5 () displays the presence of C, O, and Zn with weight percentages 28.44, 23.67 and 47.89 W%, respectively. The EDX spectrum of GO () exhibited signals for C and O with weight percentages 69.44 and 30.56 W%. EDX spectrum of the CMC/MOF-5/GO which presented the only existence of C, O, and Zn with weight percentages of 45.74, 33.63 and 20.63 W%, respectively, was indicated successful formation with high purity. The comparison of CMC/MOF-5/GO with pure CMC and GO exhibited the presence of Zn and increasing the intensity of C and O than MOF-5.

The zeta potential results of GO and CMC/MOF-5/GO were provided to confirm the drug delivery ability of materials (). The zeta potential of GO is about −16.1 mV because of –COO- groups on the GO. Due to the existence of Zn2+ in MOF-5, the zeta potential of CMC/MOF-5/GO is about +4 mV that is +20.1 mV much higher than GO.

shows the SEM images of the GO and CMC/MOF-5/GO. In can be seen the agglomeration of stacked graphene sheets due to the strong specific interactions and dispersive forces between the surface groups on the graphene-like layers. In contrast, the CMC/MOF-5/GO consists of a spongy structure with square and lamellar shapes on the graphene sheets, which was derived from the morphology of CMC and MOF-5 respectively ().

Pure TC drug was loaded in the GO and CMC/MOF-5/GO then the drug loading of carrier respectively was calculated 2.59 and 6.85 wt% using UV–Vis spectroscopy (). Since the loading of the drug was performed in the distilled water, the TC molecule is a zwitterion. In this condition, the surface of the CMC/MOF-5/GO in comparison with GO is partially positive charge that is seen in Zeta potential data. Hence, it seems there is an attractive force between TC molecules and surface of the CMC/MOF-5/GO. This was supported by TC loading data which showed an increase in the TC loading capacity of the CMC/MOF-5/GO in comparison with GO. For elucidating the potential of the synthesized carrier as an oral DDS, drug release experiment was carried out in simulated conditions with in-vivo process. The shows the release profiles of the TC-loaded GO and CMC/MOF-5/GO over 8 hours at 37oC. By comparing the charts, the amount of drug release is enhanced for CMC/MOF-5/GO than GO which might be due to the combination of CMC, MOF-5 and GO as the bio-nanocomposite structure. In the GO 0.12 mg, the drug was released at 8 hours while for CMC/MOF-5/GO the amount of drug release was 0.65 at 8 h. To reveal the drug release kinetics, the release data were fit using several models (), as described previously. The release data were best fitted with Hixson–Crowell and, to some extent, with three seconds root of mass models ().